| Project/Area Number |
17K14955
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ALS / TDP-43 / 細胞内凝集体形成 / RNA / RNA分解酵素 / RNase |
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| Outline of Final Research Achievements |
Nearly all of the amyotrophic lateral sclerosis (ALS) patients contain cytoplasmic aggregation of TDP-43 in their degenerating motor neurons. Although aggregated TDP-43 was shown to contribute to the ALS pathogenesis, the molecular mechanisms by which TDP-43 forms cytoplasmic aggregation were not fully understood. I previously found that RNAs associated with TDP-43 contributes to the formation of cytoplasmic TDP-43 aggregation. Based on this finding, I hypothesized that induced degradation of TDP-43-associated RNA led to the dissolution of already formed TDP-43 aggregation.
In this study, I developed the protein that binds to TDP-43 and induces degradation of TDP-43-associated RNAs in the cytoplasm. This protein might be effective for dissolution of TDP-43 aggregation and thus reducing the pathology caused by TDP-43 aggregation.
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| Academic Significance and Societal Importance of the Research Achievements |
筋萎縮性側索硬化症(ALS) は運動神経の変性による筋肉の萎縮により発症後数年で死に至る極めて重篤な疾患であるが、発症の詳細なメカニズムおよび治療法が確立されていない。ほぼすべてのALS患者の運動神経において観察されるTDP-43タンパク質の細胞質凝集体がALS発症に寄与すると考えられているものの、これをターゲットとした治療戦略は立てられていない。本研究では、TDP-43タンパク質の細胞質凝集体に直接作用して、それを減少させる可能性のあるタンパク質の作成に成功した。今後このタンパク質の効果と毒性を評価することで、ALSの原因療法に寄与しうる治療薬の開発につながるものと期待される。
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